Association between childhood family structure and health-related quality of life at middle age: A longitudinal study of Northern Finland Birth Cohort 1966.

AIMS: This longitudinal study evaluated the association between childhood family structure and health-related quality of life (HRQoL) at middle age. METHODS: The data on childhood family structure at the age of 14 years ('two-parent family', 'one parent not living at home/no information on father' and 'father or mother deceased') and HRQoL (measured by 15D (15-dimensional)) at the age of 46 were collected from the Northern Finland Birth Cohort 1966 using postal questionnaires. We used the binary logistic regression model to estimate the associations between childhood family structures and the lowest 15D quartile (reference: all other quartiles). The associations were adjusted for offspring mothers' factors during pregnancy (mothers' educational and occupational status). RESULTS: Of the 6375 participants, the offspring belonging to the 'one parent not living at home/no information on father' family structure subgroup had higher odds ratio of belonging to the lowest 15D quartile than the offspring of 'two-parent families' (adjusted odds ratio (OR) 1.76, 95% confidence interval (CI) 1.31-2.36, p<0.001 for females; adjusted OR 1.86, 95% CI 1.28-2.70, p=0.001 for males). There were no statistically significant associations between the 'father or mother deceased' subgroup and the lowest 15D quartile among the offspring. CONCLUSIONS: A single-parent family origin (due to reasons other than parental death) in childhood was significantly associated with impaired HRQoL at middle age. These results provide new perspectives for understanding the long-standing associations on living in a single-parent family.

Association between childhood family structure and longitudinal health behaviour changes in adulthood -Northern Finland birth cohort 1966 study.

BACKGROUND: Childhood family structure is considered to play a role in person's health and welfare. This study investigated the relationships between the longitudinal changes of adult health behaviours and childhood family structure. METHODS: From Northern Finland Birth Cohort 1966 questionnaires, we collected data on childhood family structure at the age of 14 ('two-parent family', 'one parent not living at home/no information on father', and 'father or mother deceased'), and on health behaviours (smoking, alcohol consumption and physical activity status) at the ages of 31 and 46. We used the multinomial logistic regression model to estimate the unadjusted and adjusted associations between childhood family structures and the longitudinal changes between 31 and 46 years of health behaviours (four-category variables). RESULTS: Of the study sample (n = 5431; 55.5% females), 7.1% of the offspring were represented in the 'One parent not living at home/no information on father' subgroup, 6.3% in the 'Father or mother deceased' subgroup and 86.6% in the 'Two-parent family'. 'One parent not living at home/no information on father' offspring were approximately twice as likely to smoke (adjusted OR 2.19, 95% CI 1.70-2.81) and heavily consume alcohol (adjusted OR 1.99, 95% CI 1.25-3.16) at both times in adulthood, relative to not smoking or not heavily consume alcohol, and compared with 'two-parent family' offspring. We found no statistically significant associations between childhood family structure and physical activity status changes in adulthood. CONCLUSIONS: Our findings suggest that the offspring of single-parent families in particular should be supported in early life to diminish their risk of unhealthy behaviours in adulthood.

Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46-A birth cohort study.

INTRODUCTION: The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, long-term population-based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM. MATERIAL AND METHODS: A prospective population-based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Study participants were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment. RESULTS: At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT-detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high-density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001). CONCLUSIONS: Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.

Long-term cumulative incidence of clinically diagnosed retinopathy in the Finnish Diabetes Prevention Study.

CONTEXT: Lifestyle intervention reduces the incidence of type 2 diabetes (T2D) in people with impaired glucose tolerance. OBJECTIVE: To find out whether participation in the earlier lifestyle intervention had an effect on the occurrence of clinically diagnosed retinopathy during a median of 22 years of follow-up time. METHODS: The study included 505 individuals from the Finnish Diabetes Prevention Study (DPS) (mean 55, range 40-64 years at the onset of the study) with impaired glucose tolerance who were originally randomized into the intervention (weight loss, healthy diet and physical activity (N=257) and usual care control groups (N=248). The median follow-up was 22 years. Clinical retinopathy diagnoses were obtained from the Finnish national hospital Care Register for Health. Data on glycemic parameters, serum lipids and blood pressure were available from both the intervention (median 4 years) and post-intervention period (until the year 7). RESULTS: No significant difference was found in the cumulative incidence of clinically diagnosed diabetic retinopathy between the original intervention (N=23, 8.9%) and control groups (N=19, 7.7%) during the extended follow-up (Odds ratio: 1.15, 95% confidence interval: 0.61-2.21). A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy (Hazard ratio 1.4; 1.02-1.88, 95% posterior interval, adjusted for group, age and sex). Furthermore, the incidence of retinopathy diagnosis was numerically more common among individuals who had developed diabetes during the follow-up (33/349) compared with those who had not (9/156), however, the comparison was not statistically significant (Odds ratio: 1.86, 95% confidence interval: 0.89-4.28, adjusted for group, age and sex). CONCLUSION: A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy. No evidence was found for a beneficial effect of a 4-year lifestyle intervention on the long-term occurrence of clinically diagnosed retinopathy during a median of 22-year follow-up.

Cross-sectional analysis of depressive symptom profiles and serum C-reactive protein levels: data from the Northern Finland 1966 birth cohort.

PURPOSE: Individuals with depression exhibit significantly higher levels of systemic inflammation than those without depression, particularly among those with atypical depression. However, this association has been less convincing at the population level among individuals without a formal depression diagnosis but with suggestive symptoms. Our aim was to clarify this association. MATERIALS AND METHODS: In a large birth cohort sample of the Finnish general population, we examined the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) levels in venous blood samples and atypical/non-atypical depressive symptoms using the Beck Depression Inventory-II to screen 5443 middle-aged participants. RESULTS: As expected, depressive symptoms associated to elevated hsCRP-levels compared to non-depressed. Participants with the atypical subtype of depressive symptoms (n = 84) had an odds ratio (OR) of 2.59 (95% CI 1.40-4.81) for elevated hsCRP levels compared to the non-depressed group. Similarly, our findings indicate that participants with non-atypical symptoms (n = 440) also showed an OR of 1.42 (95% CI 1.05-1.92) when compared to the non-depressed group (n = 4919). CONCLUSIONS: These results provide additional support for previous research linking depression and inflammation and add to the field with a unique and sizeable study population. Furthermore, the current results support the notion that different types of depressive symptoms may be associated with inflammatory markers in slightly different ways.

The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study.

Objective: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. Design: Bi-directional Mendelian randomisation study. Setting: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits. Participants: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits. Interventions: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking). Main outcome methods: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated. Results: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evidence for causal relations (mendelian randomisation P<0.0011) were noted between circulating cytokines, including a key role of vascular endothelial growth factor on influencing the concentrations of 10 other cytokines. Both mendelian randomisation (P<0.05) and colocalisation (posterior probability >0.5) suggested that coronary artery disease risk is increased by higher concentrations of circulating tumour necrosis factor related apoptosis-inducing ligand (TRAIL), interleukin-1 receptor antagonist (IL1RA), and macrophage colony-stimulating factor (MCSF). Conclusion: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes.

Depression mediates the relationship between alexithymia and obesity in the Northern Finland Birth Cohort 1966 (NFBC1966).

BACKGROUND: The fact that a complex relationship exists between alexithymia and body mass index (BMI) is well established, but the underlying mechanisms remain poorly understood. Here, we explore the relationship between alexithymia and depressive symptoms in relation to adiposity measures, including the direct and indirect effect of alexithymia and depressive symptoms on obesity over a 15-year time-period, in the Northern Finland Birth Cohort 1966 (NFBC1966). METHODS: The study included individuals from the Northern Finland Birth Cohort 1966 (NFBC1966) who had available data for adiposity measures (body mass index and waist-to-hip ratio), alexithymia (measured by the 20-Item Toronto Alexithymia Scale: TAS-20), depressive symptoms (measured by the 13-item depression subscale of Hopkins Symptom Checklist: HSCL-13) at age of 31 years (n = 4773) and 46 years (n = 4431). Pearson's (r) correlation, and multiple linear regression were used to investigate the relationships between alexithymia, depressive symptoms, and adiposity measures. The potential mediating role of depressive symptoms was examined via Hayes' procedure (PROCESS). RESULTS: Positive correlations were confirmed between adiposity measures (BMI and WHR) and the TAS-20 score (and its subscale), but not between obesity and HSCL-13 score. The strongest correlation was between the DIF (difficulty identifying feelings) subscale of the TAS-20 and HSCL-13 at both time points (31 y: r(3013) = 0.41, p < 0.01, 46 y: r(3013) = 0.43, p < 0.01). Depressive symptoms completely (z = 2.55 (±0.00003), p = 0.01) and partly (z = 2.16 (±0.0001), p = 0.03) mediated the alexithymia-obesity relationship over the 15-year time-period. LIMITATIONS: Other psychological and environmental factors such as interoception, dietary intake and physical activities may also play a role as a potential mediating factor in alexithymia-obesity relationship. CONCLUSIONS: Our findings provide additional insights of theoretical framework of depressive symptoms mediation effect in the relationship between alexithymia and obesity. Alexithymia and depression should, therefore, be considered in the design of future clinical obesity research.

Inflammatory Diseases, Inflammatory Biomarkers, and Alzheimer Disease: An Observational Analysis and Mendelian Randomization.

BACKGROUND AND OBJECTIVES: Whether chronic autoimmune inflammatory diseases causally affect the risk of Alzheimer disease (AD) is controversial. We characterized the relationship between inflammatory diseases and risk of AD and explored the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. METHODS: We performed observational analyses for chronic autoimmune inflammatory diseases and risk of AD using data from 2,047,513 participants identified in the UK Clinical Practice Research Datalink (CPRD). Using data of a total of more than 1,100,000 individuals from 15 large-scale genome-wide association study data sets, we performed 2-sample Mendelian randomizations (MRs) to investigate the relationships between chronic autoimmune inflammatory diseases, circulating inflammatory biomarker levels, and risk of AD. RESULTS: Cox regression models using CPRD data showed that the overall incidence of AD was higher among patients with inflammatory bowel disease (hazard ratio [HR] 1.17; 95% CI 1.15-1.19; p = 2.1 × 10-4), other inflammatory polyarthropathies and systematic connective tissue disorders (HR 1.13; 95% CI 1.12-1.14; p = 8.6 × 10-5), psoriasis (HR 1.13; 95% CI 1.10-1.16; p = 2.6 × 10-4), rheumatoid arthritis (HR 1.08; 95% CI 1.06-1.11; p = 4.0 × 10-4), and multiple sclerosis (HR 1.06; 95% CI 1.04-1.07; p = 2.8 × 10-4) compared with the age (±5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted [ORIVW] 1.23; 95% CI 1.06-1.42; p IVW = 0.007) and lower risk of Crohn disease (ORIVW 0.73; 95% CI -0.62 to 0.86; p IVW = 1.3 × 10-4). Colocalization supported a common causal single nucleotide polymorphism for MIG and Crohn disease (posterior probability = 0.74), but not AD (posterior probability = 0.03). Using a 2-sample MR approach, genetically predicted risks of inflammatory diseases were not associated with higher AD risk. DISCUSSION: Our data suggest that the association between inflammatory diseases and risk of AD is unlikely to be causal and may be a result of confounding. In support, although inflammatory biomarkers showed evidence for causal associations with inflammatory diseases, evidence was weak that they affected both inflammatory disease and AD.

Long-term effects on weight loss and maintenance by intensive start with diet and exercise.

This 36-month study aimed to determine whether exercise intervention added to weight loss treatment in the beginning or at 6 months is effective for weight loss and long-term weight maintenance. A total of 120 obese adults (body mass index >30) were randomly assigned to intensified behavioral modification (iBM), iBM+ additional exercise from 0 to 3 months (CWT1), iBM+ additional exercise from 6 to 9 months (CWT2), and a control group (CON). Questionnaires and measurements were collected at baseline, 3, 9, 24, and 36 months. The intervention consisted of an 12 months intensified weight-loss period followed by a 24 months weight-maintenance period. Eighty (67%) subjects (mean age 46.0 years, BMI 36.2) completed the trial. Compared with the control group, all three intervention groups had significant weight loss during the 36-month intervention period (p < 0.001). The achieved weight loss remained significant at 36 months in the iBM (-6.8%, p < 0.001), the CWT1 (-5.8%, p < 0.001), and the CWT2 group (-3.9%, p < 0.001). The CWT1 group showed significant reduction in waist circumference at 9 months (-11.3 cm, p < 0.001), at 24 months (-8.8 cm, p < 0.001), and at 36 months (-8.7 cm, p < 0.001). Intensified behavioral modification alone and with exercise resulted in clinically significant weight loss and long-term weight maintenance. The addition of exercise at the onset promoted greater reductions in waist circumference. In the treatment of obesity, including severe obesity, more intensive lifestyle interventions with exercise should be incorporated.

Associations between cohort study participation and self-reported health and well-being: the Northern Finland Birth Cohort 1966 Study.

AIM: The aim of this study was to explore whether active participation in a longitudinal birth cohort study is associated with study participants' health behaviour and well-being. METHODS: The subjects of this study were part of the Northern Finland Birth Cohort 1966. The follow-up data were collected through clinical examinations and questionnaires when the cohort members were 1, 14, 31 and 46 years old. In this study, cohort participation activity was divided into three categories: active, semiactive and least active. RESULTS: The total number of study participants who participated in the 46-year follow-up on both the survey and clinical trials was 6392, of which 66.5% (n=4268) participated actively in the cohort study. A total of 67.6% were female (p<0.001). Of the participants, 23.7% (n=1519) were semiactive and 9.5% (n=605) were the least active. Women who participated least actively experienced statistically significantly more depressive symptoms and poorer health, were more dissatisfied with their lives and had more addiction problems. In men, there was not a statistically significant association between participation activity and these well-being variables other than addiction problems and mental health. CONCLUSIONS: The findings indicate that participation activity is associated with better self-reported health and well-being, especially among women. With this knowledge, people can be encouraged to participate in longitudinal health research and, at the same time, may improve their own health and quality of life.

Cardiovascular disease risk and all-cause mortality associated with accelerometer-measured physical activity and sedentary time ‒ a prospective population-based study in older adults.

BACKGROUND: Low levels of physical activity (PA) and high sedentary time (ST) are common in older adults and lack of PA is a risk factor for cardiovascular disease (CVD). Knowledge about associations with accelerometer-measured PA, ST and CVD risk in older adults is insufficient. This study examines the associations of accelerometer-measured PA and ST with cardiovascular risk measured using the Framingham risk score (FRS) and all-cause mortality in older adults. METHODS: A population-based sample of 660 (277 men, 383 women) older people (mean age 68.9) participated in the Oulu45 cohort study from 2013‒2015. PA and ST were measured with wrist-worn accelerometers at baseline for two weeks. Ten-year CVD risk (%) was estimated with FRS. The data for all-cause mortality were identified from the Digital and Population Data Services Agency, Finland after an average of 6.2 years follow-up. The associations between moderate to vigorous physical activity (MVPA), light physical activity (LPA), ST and FRS were analyzed using the multivariable linear regression analysis. Associations between LPA, ST and mortality were analyzed using the Cox proportional-hazard regression models. RESULTS: Each 10 min increase in MVPA (ß = -0.779, 95% CI -1.186 to -0.371, p < 0.001) and LPA (ß = -0.293, 95% CI -0.448 to -0.138, p < 0.001) was negatively associated with FRS while a 10 min increase in ST (ß = 0.290, 95% CI 0.158 to 0.421, p < 0.001) was positively associated with FRS. After adjustment for waist circumference, only ST was significantly associated with FRS. Each 10 min increase in LPA was associated with 6.5% lower all-cause mortality risk (HR = 0.935, 95% CI 0.884 to 0.990, p = 0.020) and each 10 min increase in ST with 5.6% increased mortality risk (HR = 1.056, 95% CI 1.007 to 1.108, p = 0.025). CONCLUSION: A higher amount of daily physical activity, at any intensity level, and avoidance of sedentary time are associated with reduced cardiovascular disease risk in older people. Higher time spent in light physical activity and lower sedentary time are associated with lower all-cause mortality.

Elevated One-Hour Post-Load Glucose Is Independently Associated with Albuminuria: A Cross-Sectional Population Study.

The purpose of this study was to examine and compare the associations between albuminuria and fasting (FPG), 1 h post-load (1 h PG) and 2 h post-load plasma glucose (2 h PG) in an oral glucose tolerance test (OGTT). A total of 496 people free of known diabetes (mean age 72 years) participated in the examinations including the OGTT with plasma glucose measurements at 0, 1, and 2 h and levels of HbA1c. Albuminuria was determined by the urinary albumin-to-creatinine ratio and was defined as ≥3.0 mg/mmol. Compared with those without albuminuria, participants with albuminuria had significantly higher 1 h PG and 2 h PG levels, but not FPG or HbA1c levels. An elevated 1 h PG increased the estimated odds ratio of albuminuria more than three times in people with prediabetic 1 h PG (8.6-11.5 mmol/L: OR 3.60; 95% CI 1.70-7.64) and diabetic 1 h PG (≥11.6 mmol/L: OR 3.05; 95% CI 1.29-7.23). After adjusting for blood pressure and age, the association of elevated 1 h PG with albuminuria remained significant. Prediabetic or diabetic FPG, 2 h PG, or HbA1c did not have a statistically significant association with albuminuria. These findings suggest that 1 h PG seems to be the best glycemic parameter and is useful in recognizing persons with an elevated risk of early kidney disease due to hyperglycemia.

Association between mitochondrial DNA haplogroups J and K, serum branched-chain amino acids and lowered capability for endurance exercise.

BACKGROUND: Endurance exercise training promotes the catabolism of branched-chain amino acids (BCAAs) in skeletal muscles. We have previously shown that mitochondrial DNA (mtDNA) haplogroups J and K are markers of low responders in endurance training. In this paper, we hypothesize that BCAA catabolism is a surrogate marker of lower respiratory chain activity attributed to these haplogroups. We evaluated whether exercise-induced changes in amino acid concentrations differ between subjects harbouring mtDNA haplogroups J or K and those with non-JK haplogroups. METHODS: Finnish male conscripts (N = 633) undertook the 12-min Cooper running test at the beginning and end of their military service. The intervention during the service mainly included endurance aerobic exercise and sports-related muscle training. Concentrations of seven amino acids were analysed in the serum using a high-throughput 1H NMR metabolomics platform. Total DNA was extracted from whole blood, and restriction fragment analysis was used to determine mtDNA haplogroups J and K. RESULTS: The concentrations of the seven amino acids were higher following the intervention, with the exception of phenylalanine; interestingly, the increase in the concentrations of three BCAAs was larger in subjects with haplogroup J or K than in subjects with non-JK haplogroups (p = 0.029). MtDNA haplogroups J and K share two common nonsynonymous variants. Structural analysis based on crystallographic data on bovine complexes I and III revealed that the Leu18 variant in cytochrome b encoded by m.14798T > C may interfere with ubiquinone binding at the Qi site in complex III. CONCLUSIONS: The increase in the concentrations of serum BCAAs following exercise intervention differs between subjects harbouring mtDNA haplogroup J or K and those harbouring non-JK haplogroups. Lower response in endurance training and difference in exercise-induced increase in the concentrations of serum BCAAs suggest decreased respiratory chain activity. Haplogroups J and K share m.14798T > C in MT-CYB, which may hamper the function of complex III.

Skin cancers and their risk factors in older persons: a population-based study.

BACKGROUND: The number of skin cancer is increasing rapidly. However, little is known about the risk factors of skin cancer in older persons. Our objectives were to determine the risk factors for skin cancer or its precursors in an older population. More specifically, to study the association of new skin cancers with previous skin cancer, sex, age, Fitzpatrick's skin type, history of outdoor work and socioeconomic status (SES). METHODS: In this retrospective cross-sectional study of a large, well documented historical cohort data set a total body skin examination (TBSE) was performed for 552 participants aged between 70 and 93 years by dermatologists. The information gathered was augmented with health register data and self-reported data. The associations between skin cancer and its risk factors were studied by using the logistic regression analyses. RESULTS: According to the TBSE skin cancer/precursor was present in 25.5% of participants and was more common in males than in females (34.5% vs 20.2%, p < 0.001). Previous skin cancer increased the risk of subsequent skin cancer 2.6-fold (OR 2.56, 95% CI 1.43-4.55) and male sex nearly 2-fold (1.97, 95% CI 1.26-3.08). Specific risk factors for the first occurrence of skin cancer were male sex and outdoor work. There was also association between skin cancer and age and socioeconomic status. CONCLUSIONS: TBSE is recommend for physicians treating older persons to allow early recognition of skin cancers or their precursors. Older males need particularly close attention.

A Natural History of Erectile Dysfunction in Elderly Men: A Population-Based, Twelve-Year Prospective Study.

There is a wide variation in the development and course of erectile dysfunction (ED) in men, which confirms the need for prospective studies. We conducted a cross-sectional analysis among the general male population at the baseline (n = 359) and in a follow-up survey (n = 218) 12 years later. The prospective 12-year study included 189 men. ED was assessed using the International Index of Erectile Function questionnaire. The mean age of the participants was 62.0 years at the baseline, while at the 12-year follow-up it was 71.6 years. The crude prevalence of ED was 61.6% at the baseline and 78.9% at the follow-up, and the prevalence tended to increase with age. All of the men aged 75 years or more had at least mild ED. The incidence of ED in every thousand person years was 53.5. A total of 54.5% of the men experienced ED progression, while 39.2% reported no changes in erectile function, and 6.3% experienced ED regression during the 12-year study. The likelihood of ED progression was higher in the older compared with younger age group (odds ratio, OR 5.2 (95% CI: 1.1-26.2)), and the likelihood of ED regression was lower among men with increased depression symptoms (OR 0.3 (95% CI: 0.1-0.6)) and among men with a decreased interest in their sexual life (OR 0.1 (95% CI: 0.0-0.6)). Lifestyle factors such as the consumption of alcohol and smoking were not significantly associated with ED.

Ocular surface health of the Finnish elderly population.

PURPOSE: The aim of this study was to describe the clinical ocular surface characteristics in a population-based sample of Finnish elderly people. METHODS: This cross-sectional study included 601 subjects (335 females, 266 males) born between the years 1933-1956 and living in Savitaipale, Finland. Ocular surface health was evaluated using a comprehensive set of diagnostic tests. Previous dry eye (DE) diagnosis and history of drug treatment of DE were also recorded. Differences between sexes were estimated with Wilcoxon rank sum test and Fisher's exact test. RESULTS: Overall, 10% and 33% of people displayed signs of DE and ocular surface disease (OSD), respectively, and 30% had been previously diagnosed with DE and 36% used some form of drugs for DE. Men displayed more severe signs of meibomian gland dysfunction, blepharitis and conjunctival redness (p < 0.001), while women had higher scores in corneal staining (p = 0.005) and OSD Index (p < 0.001). CONCLUSION: Signs of OSD and DE are common among the Finnish elderly population. However, the diagnosis is affected by the diagnostic criteria used and significant differences exist between sexes. Although women were more frequently diagnosed with DE and OSD and experienced more ocular surface irritation, men had more often lid and meibomian gland-related issues. The current diagnostic criteria of DE pose a risk of misclassifying men, who commonly display less severe symptoms in comparison with women yet exhibit more severe clinical signs associated especially with the lid margin.

Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.

BACKGROUND: Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. METHODS: Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). RESULTS: There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. CONCLUSIONS: Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.

Parental separation and offspring morbidity in adulthood: a descriptive study of the Northern Finland Birth Cohort 1966.

Aims: Rates of parental separation have increased dramatically in recent decades. We evaluated the association of individuals' childhood family structure with their somatic health over 46 years of follow-up. Methods: Data were drawn from the Northern Finland Birth Cohort, an ongoing project in which 12,058 participants born in 1966 have been followed from their 24th gestational week. Based on information supplied at age 14 years, family structure was categorised as 'single-parent family' and 'two-parent family'. The anthropometric information, data from blood samples and medical history were collected from postal questionnaires and clinical examinations routinely performed at the ages of 31 and 46 years. Results: The study population comprised a total of 10,895 individuals; 85% (n=9253) were offspring of two-parent families and 15% (n=1642) of single-parent families. Type 2 diabetes (P=0.032) or prediabetes (P=0.007), psychoactive drug problems (P<0.001) and sexually transmitted diseases (P<0.001) were more common in the single-parent family group than in the participants from two-parent families. In addition, among men back diseases (P=0.002), and among women hypertension (P=0.003) and ovary infection (P=0.024) were more frequent in individuals affected by parental death than in those from two-parent families. Conclusions: Our results indicate the association of childhood family structure with offspring morbidity during 46 years' follow-up. The lifetime morbidity was observed to be higher among offspring from a single-parent family compared to two-parent family offspring. Public and scientific concern about the consequences of parental separation on the offspring' health exist, therefore support from healthcare professionals and society is warranted.

Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis.

INTRODUCTION: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. METHOD: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. RESULTS: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. CONCLUSION: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.